[Federal Register Volume 78, Number 178 (Friday, September 13, 2013)]
[Pages 56715-56717]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-22312]



Food and Drug Administration

[Docket No. FDA-2013-N-0577]

Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Requirements for 
Submission of Labeling for Human Prescription Drugs and Biologics in 
Electronic Format

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.


[[Page 56716]]

SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by October 
15, 2013.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All 
comments should be identified with the OMB control number 0910-0530. 
Also include the FDA docket number found in brackets in the heading of 
this document.

Food and Drug Administration, 1350 Piccard Dr., PI50-400B, Rockville, 
MD 20850, PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Requirements for Submission of Labeling for Human Prescription Drugs 
and Biologics in Electronic Format--(OMB Control Number 0910-0530)--

    FDA is requesting that OMB extend approval under the Paperwork 
Reduction Act (44 U.S.C. 3501-3520) for the information collection 
resulting from the requirement that the content of labeling for 
prescription drug products be submitted to FDA electronically in a form 
that FDA can process, review, and archive. This requirement was set 
forth in the final rule entitled ``Requirements for Submission of 
Labeling for Human Prescription Drugs and Biologics in Electronic 
Format'' (December 11, 2003; 68 FR 69009), which amended FDA 
regulations governing the format in which certain labeling is required 
to be submitted for FDA review with new drug applications (NDAs) (21 
CFR 314.50(l)(1)(i)), including supplemental NDAs, abbreviated new drug 
applications (ANDAs) (21 CFR 314.94(d)(1)(ii)), including supplemental 
ANDAs, and annual reports (21 CFR 314.81(b)(2)(iii)(b)) (the final rule 
also applied to certain BLAs, but the information collection for these 
requirements is not part of this OMB approval request).
    This OMB approval request is only for the burden associated with 
the electronic submission of the content of labeling. The burden for 
submitting labeling as part of NDAs, ANDAs, supplemental NDAs and 
ANDAs, and annual reports, has been approved by OMB under control 
number 0910-0001.
    We estimate that it should take applicants approximately 1.25 hours 
to convert the content of labeling from Word or PDF to structured 
labeling format (SPL) format. The main task involved in this conversion 
is copying the content from one document (Word or PDF) to another 
(SPL). Over the past few years, several enhancements have been made to 
SPL authoring software which significantly reduces the burden and time 
needed to generate well-formed SPL documents. SPL authors may now copy 
a paragraph from a Word or PDF document and paste the text into the 
appropriate section of an SPL document. In those cases where an SPL 
author needs to create a table, the table text may be copied from the 
Word or PDF document and pasted into each table cell in the SPL 
document, eliminating the need to retype any information. Enhancements 
have also been made to the software for conversion vendors. Conversion 
software vendors have designed tools which will import the Word version 
of the content of labeling and, within minutes, automatically generate 
the SPL document (a few formatting edits may have to be made).
    Based on the number of content of labeling submissions received 
during the past few years, we estimate that approximately 5,750 content 
of labeling submissions are made annually with original NDAs, ANDAs, 
supplemental NDAs and ANDAs, and annual reports by approximately 500 
applicants. Therefore, the total annual hours to convert the content of 
labeling from Word or PDF to SPL format would be approximately 7,187.50 
    Concerning costs, we conclude that there are no capital costs or 
operating and maintenance costs associated with this collection of 
information. In May 2009, FDA issued a guidance for industry entitled 
``Providing Regulatory Submissions in Electronic Format--Drug 
Establishment Registration and Listing.'' The guidance describes how to 
electronically create and submit SPL files using defined code sets and 
codes for establishment registration and drug listing information, 
including labeling. The information collection resulting from this 
guidance, discussed in the Federal Register of January 8, 2009 (74 FR 
816), has been approved by OMB under control number 0910-0045. As 
discussed in the January 8, 2009, Federal Register notice, to create an 
SPL file and submit it to FDA, a registrant would need the following 
tools: A computer, appropriate software, access to the Internet, 
knowledge of terminology and standards, and access to FDA's electronic 
submission gateway (ESG). Registrants (and most individuals) have 
computers and Internet access available for their use. If a business 
does not have an available computer or access to the Internet, free use 
of computers and the Internet are usually available at public 
facilities, e.g., a community library. In addition, there should be no 
additional costs associated with obtaining the appropriate software. In 
2008, FDA collaborated with GlobalSubmit to make available free SPL 
authoring software that SPL authors may utilize to create new SPL 
documents or edit previous versions. (Information on obtaining this 
software is explained in section IV.A of the guidance ``Providing 
Regulatory Submissions in Electronic Format--Drug Establishment 
Registration and Listing.'') In addition to the software, FDA also 
provides technical assistance and other resources, code sets and codes, 
and data standards regarding SPL files.
    After the SPL file is created, the registrant would upload the file 
through the ESG, as explained in the January 8, 2009, Federal Register 
notice. A digital certificate is needed to use the ESG. The digital 
certificate binds together the owner's name and a pair of electronic 
keys (a public key and a private key) that can be used to encrypt and 
sign documents. A fee of up to $20 is charged for the digital 
certificate and the registrant may need to renew the certificate not 
less than annually. We are not calculating this fee as a cost for this 
extension because all applicants who submit content of labeling are 
also subject to the drug establishment registration and listing 
requirements and would have already acquired the digital certificate as 
a result of the May 2009 guidance on drug establishment registration 
and listing.
    In the Federal Register of May 30, 2013 (78 FR 32392), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. There were two comments received. Both 
comments disagreed with FDA's estimate of 1.25 hours for converting the 
content of labeling to SPL format. One comment said it would take 4 to 
12 hours for experienced users to develop the initial well-formed SPL 
and 4-5 hours for an SPL update, and that these estimates vary 
depending on the complexity of the labeling metadata

[[Page 56717]]

and whether changes are necessary. The comment said that FDA also needs 
to account for the time required for validating the SPL extensible 
markup language (XML) file, including the need for using at least one 
XML validation tool to ensure that the SPL file set is well-formed and 
error-free. The comment said that copying table cells to create an SPL 
file is time consuming and prone to errors, and that software tools do 
not allow users to copy and paste the text and render it as intended in 
SPL. The comment said that most users need to apply applicable 
formatting to tables, which leads to longer conversion timelines, and 
that manually creating the SPL file and proofing the document is time-
    One comment said that updating the SPL file for submission to FDA 
when a non-annotated or partially annotated MS Word document is 
received from FDA requires a significant amount of time to identify the 
changes to the labeling. The comment said that although SPL is a useful 
and necessary format it involves extra time and costs for staying 
current with changes in terminology and software versions, and for 
conversion from another format when FDA requests documents in both MS 
Word and SPL. The comment said that maintaining multiple formats of 
labeling, negotiating FDA comments, and documenting agreements to final 
labeling is time-consuming.
    A comment requested that FDA use a single, electronic file format 
for receipt, review, and revision of labeling. The comment said that 
companies currently receive information from FDA during its review of 
labeling in many formats, including MS Word (both editable and hard-
formatted), faxes, texts, in emails, or other scanned documents with 
handwritten comments. The comment noted that each iteration of the MS 
Word document may need to be converted to SPL for submission, and that 
managing the same activities for two different formats doubles the 
work-load and causes incremental costs to be incurred by companies. The 
comment also said that there should be better document management 
(e.g., version control, tracking changes, and validation) of the MS 
Word documents. A comment said that the staffing, expertise, and 
technical support necessary to independently determine the need for a 
labeling change is costly.
    One comment preferred the use of MS Word for labeling revisions and 
negotiations with FDA, and said that until FDA is able to revise 
labeling using only SPL it should not require an SPL submission until 
14 days post-approval.
    Concerning the need for a digital certificate to use the ESG, one 
comment said that companies may need to renew the certificate ``not 
less than annually.'' The comment said that FDA should maintain an 
accurate list of acceptable digital certificate vendors and communicate 
the list to stakeholders via a formal process, as well as issue 
appropriate notice of changes. The comment noted that some companies 
received messages from FDA that one of the vendors listed as an 
approved certificate vendor was not acceptable for use for submissions 
to FDA, and, as a result, the companies purchased multiple certificates 
from different vendors in order to use the ESG.
    A comment requested clarification concerning the type of filing 
needed or anticipated by FDA to make an appropriate labeling decision. 
The comment said that the Federal Register notice is not clear about 
what type of filing is needed ``other than a CBE [change being 
effected], which will not allow the Agency adequate time to review if 
the label change is solely linked to one manufacturer or if it is 
indeed a product related safety concern applicable to an entire class 
of pharmaceuticals.''
    FDA appreciates the comments. We will respond to the issues raised 
in the comments and amend this collection if necessary as soon as we 
have gathered sufficient information to address the cost issues 
specified in the comments. The public will have an opportunity to 
comment on our response at that time.
    FDA estimates the burden of this collection of information as 

                                                     Table 1--Estimated Annual Reporting Burden \1\
                                                                                         Number of
 Content of labeling submissions in NDAs, ANDAs, supplemental NDAs      Number of      responses per     Total annual    Average burden    Total hours
                   and ANDAs, and annual reports                       respondents        response        responses       per response
                                                                                500            11.50             5750             1.25         7,187.50
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    Dated: September 6, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-22312 Filed 9-12-13; 8:45 am]